Ultrasonograph

ABSTRACT

An ultrasonograph is provided wherein the decrease of the density of the stabilized microbubble contrast agent in a desired body target area can be inhibited, radiating ultrasonic energy required for satisfactory signal-to-noise ratio and sufficient frame rate, where an ultrasonic probe transmits an ultrasonic pulse acquired by superimposing higher harmonics including a second harmonic of the fundamental onto the fundamental wave, such as a maximum positive pressure enhanced waveform or a maximum negative pressure enhanced waveform, or an acoustic pressure rise enhanced waveform or an acoustic pressure fall enhanced waveform.

This application is a 371 of PCT/JP02/00945 filed Feb. 6, 2002.

TECHNICAL FIELD

The present invention relates to an ultrasonograph for obtaining animage of the inside of a living body by transmitting/receiving anultrasonic wave to/from the living body.

BACKGROUND ART

An ultrasonograph that transmits/receives an pulsed ultrasound to/from aliving body and senses the inside of the living body is widely used inmedical diagnosis. In fields of X-ray and MRI out of image diagnosticmodalities, a contrast agent has been used for imaging of a circulatorysystem.

In the meantime, in ultrasonic diagnosis, a contrast agent has been notwidely used, however, in a few years, a contrast agent made offormulation consists of microbubbles several micrometers in sizestabilized in several methods begins to be widely used. The principle ofcontrast enhancing utilizes that a microbubble the diameter of which isapproximately 1 micron oscillates with large amplitude resonanting withan ultrasonic wave of several MHz used for ultrasonic diagnosis, and asa result, the contrast enhancement is achieved by the improvedreflection of ultrasonic wave.

The property of a contrast agent for X-ray and MRI are not affected byan irradiated electromagnetic wave or magnetic fields for imaging.However, a contrast agent made of stabilized microbubble formulation iscollapsed and eliminated by an ultrasonic wave radiated for imaging andthe performance of contrast may severely decrease. This prevents imagingwith ultrasound intense and frequent enough to obtain acceptablesignal-to-noise ratio while obtaining steady contrast enhancing effectswith microbubble based contrast agent.

On the contrary, the phenomenon that microbubble is collapsed byultrasound can be utilized to eliminate contrast agent in the region ofinterest at desired time to re-initialize the conditions for contrastenhancement. This can be also regarded as an unique advantage ofmicrobubble-based ultrasound contrast agent over contrast agents forX-ray and MRI.

Ultrasonic energy per unit time is widely used as the simplest index forexpressing the magnitude of an ultrasonic wave and generally referred toas ultrasonic intensity. Besides, recently, for a physical index showingthe possibility of cavitation by an ultrasonic wave in water or in aliving body, a mechanical index (MI) defined as an expressionMI=(maximum negative pressure)/(square root of mean frequency) has beenwidely used.

Then, in an ultrasonic diagnostic system based upon prior art, a modefor lowering the magnitude of an ultrasonic wave expressed in aboveindexes and the frequency of radiation is equipped used when the densityof a contrast agent in a living body, for example, in a desired livingarea is not to be decreased. However, problems that signal-to-noiseratio is not enough, or the temporal changes of the region of interestcannot be monitored arise due to low intensity of ultrasonic wave, orlow frequency of radiation, respectively.

In the meantime, when re-initialize the contrast enhancement conditionsby elimination of contrast agents in the region of interest in livingbody, achieved by exposing higher intensity ultrasound when required,ultrasound intensity and mechanical index should be in the safety range.This causes a problem that the re-initialization cannot be achievedwithin a period short enough to meet the requests of doctors or othermedical staffs who operate the diagnostic system in the prior art.

For prior art related to the latter problem, technique for causingcavitation at low ultrasonic intensity in water or in a living body by adevice that the second harmonic is superimposed on a fundamental waveand it is radiated and promoting acoustic chemical reaction is describedin Journal of Chemical Physics (Vol. 100, p. 18784 to p. 18789), inJournal of Acoustical Society of America (Vol. 101, p. 569 to p. 577),in IEEE Transactions on Ultrasonics, Ferroelectrics, and FrequencyControl (Vol. 43, p. 1054 to p. 1062).

However, it is technique for promoting cavitation and to solve thelatter problem, a method of relating the promotion of cavitation to thebreaking of a stabilized microbubble and methodology are required.

DISCLOSURE OF THE INVENTION

The invention is made in view of such a situation and the object is toprovide an ultrasonograph wherein first, the decrease of the density ofa stabilized microbubble contrast agent in a desired living area can beinhibited, radiating ultrasonic energy required to acquire satisfactoryimage signal-to-noise ratio and a sufficient frame rate and second, thestabilized microbubble contrast agent in the desired living area can beefficiently eliminated if necessary, inhibiting the intensity of anultrasonic wave and a mechanical index within a limit for safety.

It is indicated in the above mentioned published documents that theaction of an ultrasonic wave upon a contrast agent such as a microbubbleintroduced into water or the inside of a living body can be greatlychanged even if the intensity of the ultrasonic wave is equal whenhigher harmonics are superimposed on a fundamental wave and it isradiated.

Thus, the application of this idea to an ultrasonic pulse used fortransmission when an image is obtained is tried. When the phase iscontrolled in superimposing the second harmonic on a fundamental wave,acoustic pressure waveforms shown in FIGS. 5 to 8 described laterdetailedly, a maximum positive pressure enhanced waveform shown in FIG.5 in which the peak value on the side of positive acoustic pressure ofmaximum amplitude is enhanced, that is, is larger than the peak value onthe side of negative acoustic pressure, a maximum negative pressureenhanced waveform shown in FIG. 6 in which the peak value on the side ofnegative acoustic pressure of maximum amplitude is enhanced, that is, islarger than the peak value on the side of positive acoustic pressure, anacoustic pressure rise enhanced waveform shown in FIG. 7 and also calledN wave in which the leading edge of an ultrasonic acoustic pressurewaveform is sharper than the trailing edge and an acoustic pressure fallenhanced waveform shown in FIG. 8 and also called reverse N wave inwhich the trailing edge of an ultrasonic acoustic pressure waveform issharper than the leading edge can be produced.

FIG. 1 shows the result of theoretically predicting its behavior when amicrobubble is exposed to acoustic pressure having such a waveform bynumerical calculation and comparing with the total ultrasonic energy ofa fundamental wave and a second higher harmonic common. In FIG. 1, athick solid line denotes a case of the maximum positive pressureenhanced waveform, a thick dotted line denotes a case of the maximumnegative pressure enhanced waveform, a thin solid line denotes a case ofthe acoustic pressure rise enhanced waveform and a thin dotted linedenotes a case of the acoustic pressure fall enhanced waveform.

FIG. 1 shows that in the acoustic pressure fall enhanced waveform, themaximum surface area of an oscillating microbubble is maximum andconversely, for an area in which the intensity of an ultrasonic wave isrelatively low, in the acoustic pressure rise enhanced waveform or themaximum positive pressure enhanced waveform, the maximum surface area ofthe oscillating microbubble is minimum.

As in most stabilized microbubble formulation, a microbubble isstabilized by arranging a surface active agent or a similar substance onthe surface of the microbubble, the maximum surface area of theoscillating microbubble is considered to be a physical index of theunstableness of the microbubble by acoustic pressure. That is, it isconsidered that under a condition that the total ultrasonic energy of afundamental wave component and the second harmonic component is fixed,the acoustic pressure rise enhanced waveform or the maximum positivepressure enhanced waveform is suitable when an image is obtained,inhibiting the decrease of the density of a stabilized microbubblecontrast agent in a desired living area, and to efficiently eliminatethe stabilized microbubble contrast agent in the desired living area,the acoustic pressure fall enhanced waveform is suitable.

FIG. 2 shows the result of comparing each waveform in relation to themaximum surface area of an oscillated microbubble with a mechanicalindex common. A thick full line, a thick dotted line, a thin full lineand a thin dotted line in FIG. 2 are similar to those in FIG. 1. In thiscase, the maximum surface area of an oscillating microbubble is maximumin the maximum positive pressure enhanced waveform. Therefore, it isconsidered that to efficiently eliminate a stabilized microbubblecontrast agent in a desired living area under a condition that amechanical index is fixed, the maximum positive pressure enhancedwaveform is suitable.

As described above, the problems are solved in the invention byproducing a waveform suitable for inhibiting the decrease of the densityof the stabilized microbubble contrast agent in a desired living area bysuperimposing higher harmonics on a fundamental wave and controlling thephase of both and conversely, a waveform suitable for efficientlydecreasing and suitably using any of them if necessary.

Thereby, an ultrasonograph according to the invention is based upon anultrasonic diagnostic system for imaging of the inside of a living bodyby transmitting/receiving an ultrasonic wave to/from the living bodyinto which a contrast agent is introduced using an ultrasonic probe andis characterized in that the ultrasonic probe is configured so that ittransmits an ultrasonic pulse in which higher harmonics including atleast a second harmonic of a fundamental wave is superimposed on thefundamental wave.

Besides, the invention is based upon the configuration and ischaracterized in that an ultrasonic pulse transmitted from theultrasonic probe includes the acoustic pressure fall enhanced waveformin which the trailing edge of the ultrasonic waveform is sharper thanthe leading edge.

Besides, the invention is based upon the configuration and ischaracterized in that an ultrasonic pulse transmitted from theultrasonic probe includes the maximum positive pressure enhancedwaveform in which the peak value on the side of positive acousticpressure of maximum amplitude is larger than the peak value on the sideof negative acoustic pressure.

Besides, the invention is based upon the configuration and ischaracterized in that the acoustic pressure fall enhanced waveform andthe maximum positive pressure enhanced waveform can be switchedaccording to a transmission mode.

Besides, the invention is based upon the configuration and ischaracterized in that an ultrasonic image obtained using an ultrasonicpulse having the acoustic pressure fall enhanced waveform or the maximumpositive pressure enhanced waveform is displayed.

Besides, the invention is based upon the configuration and ischaracterized in that the contrast agent includes a microbubble and themean frequency of the fundamental wave is set to the resonance frequencyof the microbubble.

Besides, the invention is based upon the configuration and ischaracterized in that the ultrasonic pulse has a waveform acquired bysuperimposing second harmonics the phase of which is shifted by π/2 fromthe fundamental wave at a point that crosses zero on the fundamentalwave.

Besides, the invention is based upon the configuration and ischaracterized in that the ultrasonic pulse has a waveform acquired bysuperimposing second harmonics the phase of which is equal to that ofthe fundamental wave at a point that crosses zero on the fundamentalwave.

Further, the invention is based upon the configuration and ischaracterized in that for the ultrasonic pulse, a maximum positivepressure enhanced waveform in which the peak value on the side ofpositive acoustic pressure of maximum amplitude is larger than the peakvalue on the side of negative acoustic pressure, a maximum negativepressure enhanced waveform in which the peak value on the side ofnegative acoustic pressure of maximum amplitude is larger than the peakvalue on the side of positive acoustic pressure, an acoustic pressurerise enhanced waveform in which the leading edge of an ultrasonicwaveform is sharper than the trailing edge and an acoustic pressure fallenhanced waveform in which the trailing edge of the ultrasonic wave issharper than the leading edge are recorded beforehand and one waveformof them is selected and used.

Furthermore, the invention is based upon the configuration and ischaracterized in that a first mode in which an ultrasonic pulse havingthe acoustic pressure rise enhanced waveform or the maximum positivepressure enhanced waveform as a principal component is transmitted and asecond mode in which an ultrasonic pulse having the acoustic pressurefall enhanced waveform or the maximum positive pressure enhancedwaveform as a principal component is transmitted can be switched.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the maximum surface area of an oscillating microbubblecompared with the total ultrasonic energy of a fundamental wave and asecond harmonic common;

FIG. 2 shows the maximum surface area of an oscillated microbubblecompared with a mechanical index common;

FIG. 3 is a block diagram for explaining the configuration of oneembodiment of the invention;

FIG. 4 is a block diagram for explaining the configuration of anotherembodiment of the invention;

FIG. 5 shows a transmitted wave acoustic pressure waveform (1) measuredby a needle like hydrophone in the vicinity of a probe of anultrasonograph according to the invention;

FIG. 6 shows a transmitted wave acoustic pressure waveform (2) measuredby the needle like hydrophone in the vicinity of the probe of theultrasonograph according to the invention;

FIG. 7 shows a transmitted wave acoustic pressure waveform (3) measuredby the needle like hydrophone in the vicinity of the probe of theultrasonograph according to the invention;

FIG. 8 shows a transmitted wave acoustic pressure waveform (4) measuredby the needle like hydrophone in the vicinity of the probe of theultrasonograph according to the invention;

FIG. 9 shows the result (1) of measuring the distribution of theparticle diameter of a stabilized microbubble before and after theradiation of an ultrasonic wave by the ultrasonograph according to theinvention;

FIG. 10 shows the result (2) of measuring the distribution of theparticle diameter of a stabilized microbubble before and after theradiation of an ultrasonic wave by the ultrasonograph according to theinvention;

FIG. 11 shows the result (3) of measuring the distribution of theparticle diameter of a stabilized microbubble before and after theradiation of an ultrasonic wave by the ultrasonograph according to theinvention; and

FIG. 12 shows the result (4) of measuring the distribution of theparticle diameter of a stabilized microbubble before and after theradiation of an ultrasonic wave by the ultrasonograph according to theinvention.

BEST EMBODIMENTS FOR EMBODYING THE INVENTION

Referring to the drawings, embodiments of the invention will bedescribed below.

FIGS. 3 and 4 are block diagrams showing the typical configuration of anultrasonograph acquired by applying the invention to an ultrasonicdiagnostic system based upon a pulse-echo method.

In a transmit waveform controller 1, a transmit waveform is selected outof plural waveforms beforehand recorded such as acoustic pressurewaveforms shown in FIGS. 5 to 8 as examples, to describe in detail, amaximum positive-pressure enhanced waveform shown in FIG. 5 in which thepeak value on the side of positive acoustic pressure of maximumamplitude is enhanced, that is, is made larger than the peak value onthe side of negative acoustic pressure, a maximum negative-pressureenhanced waveform shown in FIG. 6 in which the peak value on the side ofthe negative acoustic pressure of maximum amplitude is enhanced, thatis, is made larger than the peak value on the side of the positiveacoustic pressure, an acoustic pressure rise enhanced waveform shown inFIG. 7 in which the leading edge of an ultrasonic acoustic pressurewaveform is sharper than the trailing edge and an acoustic pressure fallenhanced waveform shown in FIG. 8 in which the trailing edge of anultrasonic acoustic pressure waveform is sharper than the leading edge,controlled amplitude is applied to the transmit waveform and it isapplied to a drive amplifier 3. To apply directivity to a transmittedwave, delay is applied to a transmitted signal to be applied to eachelement selected by an element selecting switch 4 out of elementsforming a transducer array (an ultrasonic probe) 5 and convergenceeffect is required to be acquired, and a transmitted waveconvergence/delay control unit 2 controls the delay.

A directive ultrasonic pulse transmitted to a living body from thetransducer array 5 as described above is reflected on a tissue of theliving body and a contrast agent, a part returns to the transducer array5 again and is received by each element forming it. After each signal ofelements selected by the element selecting switch 4 out of receivedsignals is amplified by a preamplifier 6, it is converted from analog todigital (A/D) and is once stored in a received wave memory 7.

More detailedly, it is general that after each signal described above ismade to pass a TGC amplifier controlled so that an amplification factoris gradually increased depending upon time elapsed since transmissionimmediately after the preamplifier 6, it is converted from analog todigital. This is a process for keeping the amplitude of a signal at theentrance of an A/D converter in a fixed range to compensate thereduction of the amplitude of the received signal substantially inproportion to the time elapsed since transmission corresponding to theattenuation of an ultrasonic wave transmitted in the living bodysubstantially in proportion to transmitted distance. Hereby, thedeterioration of a signal dynamic range caused by the quantization ofamplitude in analog-to-digital conversion is prevented. Further, inaddition to this, aliasing caused by the quantization of a time base inthe analog-to-digital conversion can be prevented by installing a bandlimit filter before the A/D converter.

To acquire the directivity of a received wave, after delay of one typeaccording to the position of each element is once applied to a signalreceived by each element and stored in the memory 7, the signals areadded and convergence effect is required to be acquired. A received waveconvergence/delay adding unit 8 executes the processing. An optimumvalue of delay time to be applied to a signal of each element is varieddepending upon the focal length of a received wave. Besides, an optimumvalue of the focal length of a received wave for acquiring asatisfactory pulse echo image is made longer in proportion to timeelapsed since transmission and acoustic velocity. Therefore, it isdesirable that a receiving method that delay time to be applied to asignal of each element is varied according to time elapsed sincetransmission is used. This method can be relatively easily realized bycontrol in reading or writing in the configurations shown in FIGS. 3 and4 that a signal received by each element is once written to the memory,is read again and the signals are added.

In B mode of a general ultrasonic diagnostic system, the amplitude isacquired based upon a signal acquired by applying delay for converging areceived wave in a detecting process and is logarithmically compressedto be a display signal. A display signal selective creation unit 12shown in the drawings executes this processing, a scan converter 13converts it to a two-dimensional image or a three-dimensional imageaccording to circumstances and a display 14 displays it on CRT or aliquid crystal display according to circumstances.

Besides, in a harmonic imaging method, a nonlinear component isextracted from a signal acquired by applying delay for converging areceived wave and the similar processing is applied to the component tobe a display signal. Hereby, a pulse echo image in which thedistribution of a stabilized microbubble contrast agent the nonlinearreflectivity of which is large, compared with a living tissue isenhanced can be acquired. In the most basic method of the harmonicimaging method, higher harmonics generated by nonlinear effect areseparated from a fundamental wave via a bandpass filter and areextracted. However, in the ultrasonograph according to the invention, asa harmonic component is included in a transmitted signal beforehand, thebasic method in which a harmonic component separated via the bandpassfilter is used for a nonlinear component cannot be used as it is.

For a nonlinear component extracting method that does not depend upon abandpass filter, there are a pulse inversion method and an amplitudemodulation method. FIG. 3 shows one embodiment of the invention in casethese are applied.

In the amplitude modulation method, one acoustic pressure waveformacquired by superimposing higher harmonics on a fundamental wave andshown in FIGS. 5 to 8 as examples is selected, the amplitude is variedplurally and it is transmitted. To extract a nonlinear component, aprinciple that the amplitude of an echo linear component of a receivedwave is proportional to the amplitude of a transmitted wave, however,the amplitude of a nonlinear component is not proportional to theamplitude of the transmitted wave is used.

To explain a case that two amplitudes are used as an example, a linearcomponent is eliminated by once recording a signal acquired byconverging a received wave acquired by transmitting a signal of firstamplitude A1 in a memory 9, multiplying a signal acquired by converginga received wave acquired by transmitting a signal of second amplitude A2by A1/A2 and calculating difference between the multiplied signal andthe signal recorded in the memory 9, and a nonlinear component isextracted. In a normal amplitude modulation method, A1 and A2 arepositive real numbers.

In the meantime, in a pulse inversion method, a pair of real numbers theabsolute values of which are equalized by inverting each sign as A1 andA2 is used. To explain acoustic pressure waveforms shown in FIGS. 5 to 8as examples, a waveform the maximum positive pressure of which isenhanced and a waveform the maximum negative pressure of which isenhanced, and a waveform the rise of the acoustic pressure of which isenhanced and a waveform the fall of the acoustic pressure of which isenhanced have the relation of a pair of one and the other acquired byinverting one. To explain operation in this case, a linear component iseliminated by selecting one acoustic pressure waveform, once recording asignal acquired by converging a received wave acquired by transmittingthe selected acoustic pressure waveform in the memory 9 and next addinga signal acquired by converging a received wave acquired by transmittingits inverted pulse waveform and the signal recorded in the memory 9 anda nonlinear component is extracted. A display signal is acquired byapplying the processing described above to a signal acquired byexecuting such signal processing in a nonlinear component extractionunit 10.

The method of acquiring a pulse echo image by enhancing the distributionof the contrast agent utilizing a fact that the microbubble contrastagent has larger nonlinear reflectivity, compared with a living tissueis described above, however, another acoustic characteristic of themicrobubble contrast agent when the contrast agent is compared with aliving tissue is that irreversible change such as instability,disappearance, reduction and conjunction may be caused by the radiationof an ultrasonic pulse.

FIG. 4 shows another embodiment of the invention in case a pulse echoimage is acquired by enhancing the distribution of a contrast agentutilizing such a property. One acoustic pressure waveform acquired bysuperimposing higher harmonics on a fundamental wave such as theexamples shown in FIGS. 5 to 8 is selected and is transmitted in fixedamplitude plural times. To explain a case of transmitting twice as anexample, a component that does not vary is eliminated by once recordinga signal acquired by converging a received wave acquired by firsttransmission in the memory 9 and calculating difference between therecorded signal and a signal acquired by converging a received waveacquired by second transmission, and a temporal change componentcorresponding to the irreversible change of the contrast agent isextracted. When the difference is simply calculated, a signal from astationary living tissue is completely eliminated and inconvenience maybe caused when the distributional position of the contrast agent isdisplayed. This problem can be solved by not weighting a signal acquiredby first transmission and a signal acquired by second transmissioncompletely equally when the difference is calculated but increasing ordecreasing weight by a few percents. Or the problem can-be solved by notmaking a time base completely coincident when the difference iscalculated but shifting a few percents of the cycle of an ultrasonicwave. The processing described above is applied to a signal acquired byexecuting such signal processing in a temporal change component detector11 to be a display signal.

FIGS. 5 to 8 show the results of measuring the acoustic pressurewaveform of a transmitted wave when an ultrasonic wave is radiated inwater using the ultrasonograph equivalent to the embodiment of theinvention having the configuration shown in FIGS. 3 or 4 in the vicinityof the transducer array (the ultrasonic probe) by a needle likehydrophone. The hydrophone that can acquire voltage output proportionalto input acoustic pressure and equal to the input acoustic pressure in asign is used. For examples, four types of acoustic pressure waveformsacquired by shifting its phase when a second harmonic is superimposed ona fundamental wave, that is, the maximum positive-pressure enhancedwaveform shown in FIG. 5, the maximum negative-pressure enhancedwaveform shown in FIG. 6, the acoustic pressure rise enhanced waveform(N wave) shown in FIG. 7 and the acoustic pressure fall enhancedwaveform (reverse N wave) shown in FIG. 8 are shown. Each amplitude ofthe fundamental wave component and the second harmonic component isfixed.

FIGS. 9 to 12 show the distribution of the size (the particle diameter)of a microbubble before and after ultrasonic waves having the acousticpressure waveforms shown in FIGS. 5 to 8 are radiated on suspendedmicrobubbles in water by fixed frequencies. FIGS. 9 to 12 show cases inwhich the maximum positive pressure enhanced waveform shown in FIG. 5,the maximum negative pressure enhanced waveform shown in FIG. 6, theacoustic pressure rise enhanced waveform shown in FIG. 7 and theacoustic pressure fall enhanced waveform shown in FIG. 8 are used forrespective acoustic pressure waveforms. In FIGS. 9 to 12, a solid line(B) denotes a state before an ultrasonic wave is radiated, an alternatelong and short dash line (C) denotes a state after an ultrasonic wave isradiated and a dotted line (D) denotes difference between the results ofmeasurement before and after the ultrasonic wave is radiated.

In the case of any waveform, the number of microbubbles a few micron ina diameter resonated with an ultrasonic wave used in the ultrasonographthe frequency of which is approximately 2 MHz decreased. In themeantime, the number of microbubbles below 1 micron in a diameterslightly increases, however, this is considered because the agent thatstabilized a destroyed microbubble is counted.

A further comparison of the results by the four types of waveforms showsthat under a condition that the intensity of an ultrasonic wave isfixed, in the case of the acoustic pressure fall enhanced waveform(reverse N wave), microbubbles are eliminated particularly at highefficiency and conversely, in the case of the acoustic pressure riseenhanced waveform (N wave) and the maximum positive pressure enhancedwaveform, the elimination of microbubbles is remarkably inhibited. Theresult of the experiment agrees well with the result of theoreticalprediction by numerical calculation shown in FIG. 1.

As described above, when an image is obtained, keeping the stabilizedmicrobubble contrast agent in a desired living area possibly, it isadvantageous to select the acoustic pressure rise enhanced waveform, themaximum positive pressure enhanced waveform or an intermediate waveformand to acquire a pulse echo image emphasizing the distribution of thecontrast agent by extracting a temporal change component by transmittingplural times or by extracting a nonlinear component by amplitudemodulation.

Conversely, when an image is obtained, efficiently eliminating thestabilized microbubble contrast agent in a desired living area at as lowultrasonic energy as possible, it is advantageous to select the acousticpressure fall enhanced waveform and to acquire a pulse echo imageemphasizing the distribution of the contrast agent by extracting atemporal change component by transmitting plural times or by extractinga nonlinear component by amplitude modulation or pulse inversion.

Or when an image is obtained, efficiently eliminating the stabilizedmicrobubble contrast agent in a living area by the radiation of anultrasonic wave at as a low mechanical index as possible, it isadvantageous to select the maximum positive pressure enhanced waveformand to acquire a pulse echo image emphasizing the distribution of thecontrast agent by extracting a temporal change component by transmittingplural times or by extracting a nonlinear component by amplitudemodulation.

It is considered that ultrasonic image diagnosis utilizing thecharacteristic of the stabilized microbubble contrast agent is enabledby suitably switching the contrast agent keeping image obtaining modeand the contrast agent eliminating imaging mode using the ultrasonographhaving the configuration shown in FIG. 3 or 4 to which the invention isapplied.

INDUSTRAIL AVAILABILITY

As described above, according to the invention, the ultrasonographwherein ultrasonic image obtaining at satisfactory image signal-to-noiseratio and an enough frame rate is enabled, inhibiting the decrease ofthe density of the stabilized microbubble contrast agent in a desiredliving area by controlling the waveform of a transmitted wave andbesides, the stabilized microbubble contrast agent in the desired livingarea can be efficiently eliminated if necessary, keeping the intensityof an ultrasonic wave and a mechanical index within a limit for safetycan be realized. Therefore, the meaning in medical care and industry ofthe invention can be said to be large.

1. An ultrasonograph for obtaining an image of the inside of a living body by transmitting/receiving an ultrasonic wave to the living body into which a contrast agent is introduced comprising: an ultrasonic probe transmitting a first ultrasonic pulse and a second ultrasonic pulse, generated by superimposing higher harmonics including at least a second harmonic of a fundamental wave; a memory for recording a first converted signal acquired by converging the signal acquired by transmission of the first ultrasonic pulse; and a temporal change component detector for extracting a temporal change component corresponding to an irreversible change of the contrast agent caused by radiation of the ultrasonic pulse, wherein: the first ultrasonic pulse is an acoustic pressure rise enhanced waveform in which a leading edge of an ultrasonic acoustic pressure waveform is sharper than a trailing edge of the ultrasonic acoustic pressure waveform, the second ultrasonic pulse is an acoustic pressure fall enhanced waveform in which a trailing edge of an ultrasonic acoustic pressure waveform is sharper than a leading edge the ultrasonic acoustic pressure waveform, the ultrasonic probe transmits the first ultrasonic pulse or the second ultrasonic pulse with switching an ultrasonic acoustic pressure waveform, the temporal change component detector calculates a difference between the first converted signal recorded in the memory and a second converted signal acquired by converging the signal acquired by transmission of the second ultrasonic pulse as the temporal change component, and the temporal change component detector adds variable weight to the first converted signal and/or the second converted signal.
 2. An ultrasonograph according to claim 1, wherein: an ultrasonic pulse transmitted from the ultrasonic probe includes a maximum positive pressure enhanced waveform in which the peak value on the side of positive acoustic pressure of maximum amplitude is larger than the peak value on the side of negative acoustic pressure.
 3. An ultrasonograph according to claim 1, wherein: an ultrasonic pulse transmitted from the ultrasonic probe includes a maximum negative pressure enhanced waveform in which the peak value of the side of negative acoustic pressure of maximum amplitude is larger than the peak value on the side of positive acoustic pressure.
 4. An ultrasonograph according to claim 1, wherein: the contrast agent includes microbubbles; and the mean frequency of the fundamental wave is set to the resonance frequency of the microbubble at the mean diameter of microbubbles introduced.
 5. An ultrasonograph according to claim 1, wherein: the ultrasonic pulse has a waveform generated by superimposing a second harmonic the phase of which is shifted by .pi./2 at a point that crosses zero from the fundamental wave on the fundamental wave.
 6. An ultrasonograph according to claim 1, wherein: the ultrasonic pulse has a waveform generated by superimposing a second harmonic the phase of which is equal to that of the fundamental wave at a point that crosses zero on the fundamental wave.
 7. An ultrasonic apparatus for obtaining an image of the inside of a living body by transmitting/receiving an ultrasonic wave to the living body into which a contrast agent is introduced comprising: an ultrasonic probe transmitting a first ultrasonic pulse and a second ultrasonic pulse, generated by superimposing higher harmonics including at least a second harmonic of fundamental wave on the fundamental wave a memory for recording a first converted signal acquired by converging the signal acquired by transmission of the first ultrasonic pulse; and temporal change component detector extracting a temporal change component corresponding to the irreversible change of the contrast agent caused by radiation of the ultrasonic pulse, wherein: an ultrasonic pulse transmitted from the ultrasonic probe includes a maximum positive pressure enhanced waveform in which the peak value on the side positive acoustic pressure of maximum amplitude is larger than the peak value on the side of negative acoustic pressure, an ultrasonic pulse transmitted from the ultrasonic probe includes a maximum negative pressure enhanced waveform in which the peak value on the side of negative acoustic pressure of maximum amplitude is larger than the peak value on the side of positive acoustic pressure, the ultrasonic proved transmit the first ultrasonic pulse or the second ultrasonic pulse with switching an ultrasonic acoustic pressure waveform the temporal change component detector calculates a difference between the first converted signal recorded in the memory and a second converted signal acquired by converging the signal acquired by transmission of the second ultrasonic pulse as the temporal change component; and the temporal change component detector adds variable weight to the first converted signal and/or the second converted signal. 